Fear of Falling and Balance Confidence in Older Adults with Diabetes Mellitus

Several determinants of fear of falling (FoF) and low balance confidence overlap with the consequences/complications of diabetes mellitus (DM). FoF is strongly associated with low balance confidence, and balance confidence mediates the relationship between FoF and balance and physical function. The purpose of this thesis was two-fold: (1) to examine the prevalence, severity and determinants of FoF in older adults (aged≥65) with DM, and (2) to evaluate the validity of the short version of the Activities-specific Balance Confidence scale (ABC-6) and its association with balance and postural control in older adults with DM. Three separate studies were conducted of older adults with DM (DM-group) and without DM (noDM-group). Study I revealed that although FoF prevalence adjusted for age and sex was not different between-groups, the DM-group had 8.8% fewer participants in the low and 8.4% more in the high Falls-Efficacy Scale International categories when compared to the noDM-group. Higher FoF severity in the DM-group was associated with poor physical performance, being female, fall history and clinical depressive symptoms. Study II provided evidence of convergent, discriminant and concurrent validity of the ABC-6 for use in older adults with DM with and without diabetic peripheral neuropathy (DPN). Notably, the ABC-6 was more sensitive in detecting subtle differences in balance confidence between the DM-group and noDM-group when compared to the original ABC scale (ABC-16), and can be administered in less time. Study III explored balance confidence (ABC-6) and its association with balance and postural control in older adults with DM. Subtle differences in axial segmental control (i.e., lower trunk roll velocity and higher head-trunk correlations) while walking and lower balance confidence were apparent in the DM-group, even in the absence of DPN, when compared to the noDM-group. Balance confidence partially explained the variance in head-trunk stiffening between-groups, and consequently low balance confidence in older adults with DM may contribute to the dependence on postural control strategies that are normally only utilized in high-risk situations. Findings from this thesis will help to guide the development of protocols for screening and intervention recommendations of patient education and targeted rehabilitation programs for older adults with DM.

ENVIRONMENTAL INFLUENCES AND EPIGENETIC MECHANISMS IN RISK FOR DEPRESSION

Genetic and environmental factors interact to influence vulnerability for internalizing psychopathology, including Major Depressive Disorder (MDD). The mechanisms that account for how environmental stress can alter biological systems are not yet well understood yet are critical to develop more accurate models of vulnerability and targeted interventions. Epigenetic influences, and more specifically, DNA methylation, may provide a mechanism by which stress could program gene expression, thereby altering key systems implicated in depression, such as frontal-limbic circuitry and its critical role in emotion regulation. This thesis investigated the role of environmental factors from infancy and throughout the lifespan affecting the serotonergic (5-HT) system in the vulnerability to and treatment of depression and anxiety and potential underlying DNA methylation processes. First, we investigated the contributions of additive genetic vs. environmental factors on an early trait phenotype for depression (negative emotionality) in infants and their stability over time in the first 2 years of life. We provided evidence of the substantial contributions of both genetic and shared environmental factors to this trait, as well as genetically- and environmentally- mediated stability and innovation. Second, we studied how childhood environmental stress is associated with peripheral DNA methylation of the serotonin transporter gene, SLC6A4, as well as long-term trajectories of internalizing behaviours. There was a relationship between childhood psychosocial adversity and SLC6A4 methylation in males, as well as between SLC6A4 methylation and internalizing trajectory in both sexes. Third, we investigated changes in emotion processing and epigenetic modification of the SLC6A4 gene in depressed adolescents before and after Mindfulness-Based Cognitive Therapy (MBCT). The alterations from pre- to post-treatment in connectivity between the ACC and other network regions and SLC6A4 methylation suggested that MBCT may work to optimize the connectivity of brain networks involved in cognitive control of emotion as well as also normalize the relationship between SLC6A4 methylation and activation patterns in frontal-limbic circuitry. Our results from these three studies strengthen the theory that environmental influences are critical in establishing early vulnerability factors for MDD, driving epigenetic processes, and altering brain processes as an individual undergoes treatment, or experiences relapse.